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TitleChAdOx1 interacts with CAR and PF4 with implications for thrombosis with thrombocytopenia syndrome.
Journal, issue, pagesSci Adv, Vol. 7, Issue 49, Page eabl8213, Year 2021
Publish dateDec 3, 2021
AuthorsAlexander T Baker / Ryan J Boyd / Daipayan Sarkar / Alicia Teijeira-Crespo / Chun Kit Chan / Emily Bates / Kasim Waraich / John Vant / Eric Wilson / Chloe D Truong / Magdalena Lipka-Lloyd / Petra Fromme / Josh Vermaas / Dewight Williams / LeeAnn Machiesky / Meike Heurich / Bolni M Nagalo / Lynda Coughlan / Scott Umlauf / Po-Lin Chiu / Pierre J Rizkallah / Taylor S Cohen / Alan L Parker / Abhishek Singharoy / Mitesh J Borad /
PubMed AbstractVaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory ...Vaccines derived from chimpanzee adenovirus Y25 (ChAdOx1), human adenovirus type 26 (HAdV-D26), and human adenovirus type 5 (HAdV-C5) are critical in combatting the severe acute respiratory coronavirus 2 (SARS-CoV-2) pandemic. As part of the largest vaccination campaign in history, ultrarare side effects not seen in phase 3 trials, including thrombosis with thrombocytopenia syndrome (TTS), a rare condition resembling heparin-induced thrombocytopenia (HIT), have been observed. This study demonstrates that all three adenoviruses deployed as vaccination vectors versus SARS-CoV-2 bind to platelet factor 4 (PF4), a protein implicated in the pathogenesis of HIT. We have determined the structure of the ChAdOx1 viral vector and used it in state-of-the-art computational simulations to demonstrate an electrostatic interaction mechanism with PF4, which was confirmed experimentally by surface plasmon resonance. These data confirm that PF4 is capable of forming stable complexes with clinically relevant adenoviruses, an important step in unraveling the mechanisms underlying TTS.
External linksSci Adv / PubMed:34851659 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution1.59 - 3.07 Å
Structure data

24408

7rd1

EMDB-24408, PDB-7rd1:
The Capsid Structure of the ChAdOx1 viral vector/chimpanzee adenovirus Y25
Method: EM (single particle) / Resolution: 3.07 Å

PDB-7op2:
Chadox1/ Chimpanzee adenovirus Y25 fiber knob protein
Method: X-RAY DIFFRACTION / Resolution: 1.59 Å

Chemicals

ChemComp-CA:
Unknown entry

ChemComp-EDO:
1,2-ETHANEDIOL / Ethylene glycol

ChemComp-TRS:
2-AMINO-2-HYDROXYMETHYL-PROPANE-1,3-DIOL / pH buffer*YM / Tris

ChemComp-HOH:
WATER / Water

Source
  • chimpanzee adenovirus y25
KeywordsVIRAL PROTEIN / Fiber knob / adenovirus / fiber protein / spike / fiber / chimpanzee adenovirus / simian adenovirus / ChAdOx1 / ChAd-Y25 / Y25 / Chimp Ad / ChAdV-Y25 / cell binding / CAR / VIRUS / vaccine vector / DNA virus / AdV / adenovirus Y25 / viral vector / dsDNA virus / icosahedral / chimpanzee adenovirus Y25 / Y-25 / Y 25 / ChAdV

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